Goodlad J R, Macartney J C
Department of Histopathology, UMDS, London, GB.
Eur J Immunol. 1995 Jul;25(7):1918-26. doi: 10.1002/eji.1830250719.
Although the nature of the germinal center reaction during responses to T-dependent antigens has been well documented, much less is known regarding the relationship between germinal centers and T-independent antigens. In this study, germinal-center cell proliferation was determined at specific time points in spleens of C3H/HeN mice following immunization with either the type-1, T-independent antigen dinitrophenol-lipopolysaccharide (DNP-LPS), or the type-2, T-independent antigen DNP-Ficoll. A stathmokinetic technique was employed to assess proliferation in terms of germinal center cell birth rate and morphometry was used to measure actual growth and regression of the germinal center cell population. An estimate of the absolute rate of germinal-center (GC) cell proliferation was derived from these two values. In addition, immunohistochemistry was performed to correlate changes in GC cell proliferation with the presence or absence of antigen within GC. Following immunization with both antigens, there was an initial reduction of proliferation within pre-existing germinal centers which manifested as either GC dissociation (DNP-LPS) or a suppression of birth rates (DNP-Ficoll). This was followed by a period of increased GC cell proliferation in animals immunized with DNP-LPS, but not in those exposed to DNP-Ficoll. GC cell proliferation was then measured in mice treated with cyclosporin A from 1 day before to 2 days after immunization with DNP-LPS. In these animals, the expected increase in GC cell birth rates did not take place. Immunohistochemistry showed that DNP-Ficoll and DNP-LPS were present in GC from 1 day after immunization until the end of the experiment on day 7. Treatment with cyclosporin A did not affect the deposition of DNP-LPS in GC. These results show that only some T-independent antigens are able to stimulate GC cell proliferation, and we propose that this is related to their ability to recruit precursors of GC B cells into the GC reaction. In addition, the results indicate that GC proliferation seen in response to a so-called T-independent antigen is at least partly driven by T cell-derived cytokines.
尽管在对T细胞依赖性抗原的应答过程中生发中心反应的性质已有充分记载，但关于生发中心与T细胞非依赖性抗原之间的关系却知之甚少。在本研究中，用1型T细胞非依赖性抗原二硝基苯酚-脂多糖（DNP-LPS）或2型T细胞非依赖性抗原DNP-菲可（Ficoll）免疫C3H/HeN小鼠后，在特定时间点测定脾脏中生发中心细胞的增殖情况。采用有丝分裂抑制技术根据生发中心细胞出生率评估增殖，并用形态计量学测量生发中心细胞群体的实际生长和消退情况。从这两个值得出生发中心（GC）细胞增殖绝对速率的估计值。此外，进行免疫组织化学以将GC细胞增殖的变化与GC内抗原的存在与否相关联。用两种抗原免疫后，先前存在的生发中心内的增殖最初均降低，表现为GC解离（DNP-LPS）或出生率受抑制（DNP-Ficoll）。随后，用DNP-LPS免疫的动物出现一段GC细胞增殖增加的时期，而用DNP-Ficoll免疫的动物则未出现。然后在从用DNP-LPS免疫前1天至免疫后2天用环孢素A处理的小鼠中测量GC细胞增殖。在这些动物中，未出现预期的GC细胞出生率增加。免疫组织化学显示，从免疫后1天直至实验第7天结束，DNP-Ficoll和DNP-LPS均存在于GC中。用环孢素A处理不影响DNP-LPS在GC中的沉积。这些结果表明，只有一些T细胞非依赖性抗原能够刺激GC细胞增殖，我们认为这与其将GC B细胞前体募集到GC反应中的能力有关。此外，结果表明，对所谓T细胞非依赖性抗原的应答中所见的GC增殖至少部分由T细胞衍生的细胞因子驱动。
